Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The promyelocytic leukemia protein stimulates SUMO conjugation in yeast

Oncogene volume 25, pages 2999–3005 (2006)Cite this article

Abstract

The promyelocytic leukemia gene was first identified through its fusion to the gene encoding the retinoic acid receptor alpha (RARα) in acute promyelocytic leukemia (APL) patients. The promyelocytic leukemia gene product (PML) becomes conjugated in vivo to the small ubiquitin-like protein SUMO-1, altering its behavior and capacity to recruit other proteins to PML nuclear bodies (PML-NBs). In the NB4 cell line, which was derived from an APL patient and expresses PML:RARα, we observed a retinoic acid-dependent change in the modification of specific proteins by SUMO-1. To dissect the interaction of PML with the SUMO-1 modification pathway, we used the budding yeast Saccharomyces cerevisiae as a model system through expression of PML and human SUMO-1 (hSUMO-1). We found that PML stimulated hSUMO-1 modification in yeast, in a manner that was dependent upon PML's RING-finger domain. PML:RARα also stimulated hSUMO-1 conjugation in yeast. Interestingly, however, PML and PML:RARα differentially complemented yeast Smt3p conjugation pathway mutants. These findings point toward a potential function of PML and PML:RARα as SUMO E3 enzymes or E3 regulators, and suggest that fusion of RARα to PML may affect this activity.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

APL:

acute promyelocytic leukemia

ATRA:

all-trans-retinoic acid

PML:

promyelocytic leukemia gene product

PML-NBs:

PML-nuclear bodies

RARα:

retinoic acid receptor alpha

SDS–PAGE:

SDS–polyacrylamide gel electrophoresis

SUMO:

small ubiquitin-like modifier

References

  • Azuma Y, Arnaoutov A, Dasso M . (2003). J Cell Biol 163: 477–487.

  • Azuma Y, Tan SH, Cavenagh MM, Ainsztein AM, Saitoh H, Dasso M . (2001). FASEB J 15: 1825–1827.

  • Bernardi R, Pandolfi PP . (2003). Oncogene 22: 9048–9057.

  • Borden KL . (2002). Mol Cell Biol 22: 5259–5269.

  • Chen XL, Reindle A, Johnson ES . (2005). Mol Cell Biol 25: 4311–4320.

  • Dohmen RJ, Stappen R, McGrath JP, Forrova H, Kolarov J, Goffeau A et al. (1995). J Biol Chem 270: 18099–18109.

  • Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN et al. (1999). J Cell Sci 112 (Part 3): 381–393.

  • Goddard AD, Borrow J, Solomon E . (1992). Leukemia 6 (Suppl 3): 117S–119S.

  • Hochstrasser M . (2000). Nat Cell Biol 2: E153–E157.

  • Hochstrasser M . (2001). Cell 107: 5–8.

  • Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T et al. (1999). J Cell Biol 147: 221–234.

  • Jensen K, Shiels C, Freemont PS . (2001). Oncogene 20: 7223–7233.

  • Johnson ES . (2004). Annu Rev Biochem 73: 355–382.

  • Johnson ES, Gupta AA . (2001). Cell 106: 735–744.

  • Johnson ES, Schwienhorst I, Dohmen RJ, Blobel G . (1997). EMBO J 16: 5509–5519.

  • Kamitani T, Kito K, Nguyen HP, Wada H, Fukuda-Kamitani T, Yeh ET . (1998). J Biol Chem 273: 26675–26682.

  • Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A et al. (2001). J Exp Med 193: 1361–1371.

  • Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM . (1999). Proc Natl Acad Sci USA 96: 11364–11369.

  • Melnick A, Licht JD . (1999). Blood 93: 3167–3215.

  • Muller S, Matunis MJ, Dejean A . (1998). EMBO J 17: 61–70.

  • Negorev D, Maul GG . (2001). Oncogene 20: 7234–7242.

  • Quimby BB, Wilson CA, Corbett AH . (2000). Mol Biol Cell 11: 2617–2629.

  • Saitoh H, Sparrow DB, Shiomi T, Pu RT, Nishimoto T, Mohun TJ et al. (1998). Curr Biol 8: 121–124.

  • Seufert W, Futcher B, Jentsch S . (1995). Nature 373: 78–81.

  • Strudwick S, Borden KL . (2002). Leukemia 16: 1906–1917.

  • Strunnikov AV, Aravind L, Koonin EV . (2001). Genetics 158: 95–107.

  • Takahashi Y, Iwase M, Konishi M, Tanaka M, Toh-e A, Kikuchi Y . (1999). Biochem Biophys Res Commun 259: 582–587.

  • Takahashi Y, Kahyo T, Toh EA, Yasuda H, Kikuchi Y . (2001). J Biol Chem 276: 48973–48977.

  • Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M et al. (1994). Cell 76: 345–356.

  • Zhao X, Blobel G . (2005). Proc Natl Acad Sci USA 102: 4777–4782.

  • Zhong S, Muller S, Ronchetti S, Freemont PS, Dejean A, Pandolfi PP . (2000). Blood 95: 2748–2752.

Download references

Acknowledgements

This work is dedicated to Byrn Burch who died of leukemia on October 17, 2002. This work was supported by the Intramural Research Program of the NICHD/NIH. BB Quimby was supported by a Pharmacology Research Associate Training (PRAT) fellowship. Studies on PML were initiated with support from HFSP Research Grant RG0229/1999-M.

Author information

Author notes

  1. T Anan

    Present address: Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan

Authors and Affiliations

  1. Section on Cell Cycle Regulation, Laboratory of Gene Regulation and Development, NICHD/NIH, Bethesda, MD, USA

    B B Quimby, T Anan & M Dasso

  2. Unit on Chromosome Structure and Function, Laboratory of Gene Regulation and Development, NICHD/NIH, Bethesda, MD, USA

    V Yong-Gonzalez & A V Strunnikov

Authors
  1. B B Quimby
    View author publications

    Search author on:PubMed Google Scholar

  2. V Yong-Gonzalez
    View author publications

    Search author on:PubMed Google Scholar

  3. T Anan
    View author publications

    Search author on:PubMed Google Scholar

  4. A V Strunnikov
    View author publications

    Search author on:PubMed Google Scholar

  5. M Dasso
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to M Dasso.

Additional information

Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quimby, B., Yong-Gonzalez, V., Anan, T. et al. The promyelocytic leukemia protein stimulates SUMO conjugation in yeast. Oncogene 25, 2999–3005 (2006). https://doi.org/10.1038/sj.onc.1209335

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1209335

Keywords

This article is cited by

Search

Advanced search

Quick links